New Research Suggests Two Brain Areas Critical for Short-term Memory

May 13, 2004

Research in animals has revealed new information about how animals and humans may store and retrieve short-term memories, say researchers from Wake Forest University Baptist Medical Center.

“For the first time, we’ve found that two different areas of the brain share the function of storing and remembering events for short-term memory,” said Sam Deadwyler, Ph.D., lead researcher. “These new findings broaden our understanding of how memory works.”

Deadwyler and co-investigator Robert Hampson, Ph.D., showed that the hippocampus, a structure long believed to be important for short-term memory, shares this function with another adjacent brain area, the subiculum. The research, reported in the current issue of Neuron, shows that both structures are required to process information correctly.

Knowing more about memory – and what goes wrong in conditions such as Alzheimer’s disease – could lead to more sensitive tests for early diagnosis, as well as new drugs to enhance and recover memory, said Deadwyler. In addition, the findings that two brain areas act together to establish and retrieve short-term memories suggests the possibility that humans could be retrained to use one area if the other is damaged or diseased.

“Surprisingly, we found that the shortest memories were controlled almost exclusively by the subiculum, which is exactly opposite from what was previously believed,” said Deadwyler. “For the first 10 to 15 seconds of the task used to examine this in rats, we found that the memory function of the hippocampus actually shuts off.”

Using multiple electrodes smaller than the size of a human hair, the researchers recorded activity in the hippocampus and subiculum as rats performed a memory task. The results showed that both brain structures “encode” or “remember” information, but they do it at different times.

For the memory task, rats were randomly presented either a “right” of “left” lever. With food as an incentive, the rat pressed the lever and then had to perform another behavior on the opposite side of the cage for 1 second to 30 seconds as a distraction. When the animal returned after the delay, both the “right” and “left” levers were showing. To get the task correct, the rat now had to press the lever opposite from the one selected at the beginning of the trial.

Electrode recordings of cell activity in both brain areas unexpectedly showed that when the imposed delay was less than 15 seconds, only the subiculum recorded the information. But, when the delay was longer, the subiculum became inactive while the hippocampus switched on and took over control of the memory requirements of the task.

The research also revealed another important finding about the hippocampus. When it switched on to complete the trial, the memory was biased by past experience. This strategy allowed the hippocampus to anticipate future events based on past outcomes.

With the rat trials, the hippocampus did not start from scratch. Because of this strategy in some cases it would “expect” the trials to alternate “left,” then “right,” and fired cells to remember the alternate lever even before the trial began.

“When the hippocampus relies on previous experience, and doesn’t use current events, the rat can get the task wrong because the anticipatory firing is actually controlling the animal’s behavior,” said Hampson.

In humans, this is similar to someone who takes the same highway exit each day to get to work. He may end up taking that route even when he’s not supposed to – such as on a day he needed to go to the dentist before work.

“When this happens, you’re using a behavioral pattern that is remembered by your hippocampus,” said Deadwyler. “When you get in your car in the morning, you trigger that pattern and your hippocampus then takes over. Based on familiar landmarks, it then guides you toward your destination. But, you’re acting in accordance with what your ‘memory’ is telling you instead of what is actually going on in the real world around you, and you miss the turn.”

The researchers hope to continue the work to learn more about how the hippocampus and subiculum work together with other brain regions to establish more permanent memories.

The research was funded by grants from the National Institutes of Health (National Institute on Drug Abuse and National Institute of Mental Health).

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Contacts: Karen Richardson,; Shannon Koontz,; at 336-716-4587.

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